Psychopharmacol Bull. 2017;47(3):8–16. Original Presentations Key Words: antipsychotic agents, cognition, community mental health centers, disease progression, hospitalization, myelin sheath, paliperidone palmitate, psychotic disorders, random allocation, schizophrenia, treatment outcome
Baseline Demographics and Characteristics From a Paliperidone Palmitate Study in Subjects with Recent-Onset Schizophrenia or Schizophreniform Disorder By Brianne Brown, Larry Alphs, Ibrahim Turkoz, Yong Yue
Introduction • Early and effective treatment of schizophrenia may slow disease progression and improve overall patient outcomes.1 In addition, interventions specifically targeting cognitive deficits may prevent chronic disability2 • In individuals with first-episode schizophrenia, greater improvements have been reported with long-acting injections vs oral antipsychotics (APs)3,4 • The Disease Recovery Evaluation and Modification (DREaM) study is examining whether paliperidone palmitate once-monthly (PP1M) followed by paliperidone palmitate once-every-3-months (PP3M) injections can slow disease progression and possibly modify the course of schizophrenia compared with oral APs in subjects with recent-onset psychosis (schizophrenia or schizophreniform disorder) by tracking changes in cognition, functioning, and intracortical myelin volume and by tracking treatment failures • Key innovations of the DREaM study include double randomization of matched-control subjects in a delayed-start design. This study design is used to distinguish between a treatment’s effect on symptom improvement and potential disease modification5 • We describe the baseline demographics and clinical characteristics of early enrollees to the DREaM study Presented at the American Psychiatric Association Annual Meeting, May 20–24, 2017, San Diego, CA. Drs. Brown, Alphs, Yue, Janssen Scientific Affairs, LLC, Titusville, NJ; Dr. Turkoz, Janssen Research & Development, LLC, Titusville, NJ. To whom correspondence should be addressed: Dr. Larry Alphs, MD, PhD, Therapeutic Team Leader: Psychiatry, Janssen Scientific Affairs, LLC, 1125 Trenton-Harbourton Rd–A32404, Titusville, NJ 08560. E-mail: [email protected]
8 • P sychopharmacol B ull : Vol. 47 · No. 3
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Baseline Demographics and Characteristics From a Paliperidone Palmitate Study
• These characteristics are compared to those of subjects enrolled in a trial evaluating a similar population: the Recovery After an Initial Schizophrenia Episode (RAISE) study, a multisite, randomized controlled trial in subjects with first-episode psychosis6 Methods Study Designs DREaM (NCT02431702) • DREaM is a prospective, matched-control, double-randomized, openlabel, flexible-dose study in subjects with recent-onset schizophrenia or schizophreniform disorder that compares disease progression and disease interception following treatment with PP1M/PP3M or oral APs • Subjects aged 18 to 35 years with a DSM-5 diagnosis of schizophrenia or schizophreniform disorder and first psychotic episode within 2 years of enrollment are eligible • Participating sites include academic- and community-based clinics both with and without established clinics that specialize in firstepisode psychosis • DREaM includes three treatment phases (Figure 1)
9 Brown, Alphs, Turkoz, et al.
RAISE • Subjects were aged 15 to 40 years with a DSM-IV diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder, brief psychotic disorder, or psychotic disorder not otherwise specified • All participants had experienced only one episode of psychosis and had received ⩽6 months of AP medications in their lifetime • Participating sites included 34 community mental health centers in the United States • Academic centers or sites with existing first-episode psychosis programs were excluded from participation6 DREaM Screening/Baseline Eff icacy Assessments • The following assessments were performed at either screening (visit 1) or baseline (Part 1: visit 2, day 1): • Baseline demographics and clinical characteristics • MATRICS Consensus Cognitive Battery (MCCB)7: Measured key cognitive domains relevant to schizophrenia and related disorders • Personal and Social Performance (PSP) scale8: Assessed personal and social functioning within the past month P sychopharmacol B ull : Vol. 47 · No. 3
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Baseline Demographics and Characteristics From a Paliperidone Palmitate Study FIGURE 1
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Notes: In Part 1, subjects who tolerate paliperidone extended-release but whose clinician finds it inadequately efficacious (per clinical judgment) may be switched to another protocol-specified oral AP: aripiprazole, haloperidol, olanzapine, perphenazine, quetiapine, or risperidone. In Parts 2 and 3, 9-month paliperidone palmitate treatment = PP1M for 4 months (five injections) followed by PP3M for 5 months (two injections).
• Clinical Global Impression of Severity (CGI-S) scale9: Rated the severity of the subject’s overall clinical condition on a 7-point scale (1 = not ill, 7 = extremely ill) • Medication Satisfaction Questionnaire (MSQ) 10,11: Rated selfreported satisfaction with current AP treatment on a 7-point Likert scale (1 = extremely dissatisfied, 7 = extremely satisfied) • Clinician-Rated Dimensions of Psychosis Symptom Severity (CRDPSS)12: An 8-item measure that assesses the severity of mental health symptoms that are important across psychotic disorders, such as delusions, hallucinations, disorganized speech, abnormal psychomotor behavior, negative symptoms, impaired cognition, depression, and mania, on a 5-point scale (0 = none, 4 = present and severe) Statistical Analyses • Baseline demographics and clinical characteristics were generated for the DREaM study using descriptive statistics. In some cases where data were available, demographics and clinical characteristics were compared between the DREaM and RAISE studies • Study comparisons for available data points were carried out using either the chi-squared test for categorical data or the t-test for continuous data points P sychopharmacol B ull : Vol. 47 · No. 3
PB-Brown.indd 10
8/4/2017 3:38:33 PM
Baseline Demographics and Characteristics From a Paliperidone Palmitate Study TABLE 1
Baseline Demographics in the DREaM and RAISE Studies
BASELINE CHARACTERISTIC
Age, y, mean (SD) Sex, male, n (%) Race, n (%) White Black Other Missing data Ethnicity, n (%) Hispanic or Latino Living status, n (%) Independent living Supported or structured With family/friends Homeless/other Patient education, n (%) Some college or higher Completed high school Some high or grade school No school or unknown Maternal education, n (%) Some college or higher Completed high school Some high or grade school No school or unknown
Abbreviation: SD, standard deviation.
DREaM: ENROLLED SUBJECTS N = 96
RAISE: FINAL POPULATION6 N = 404
47 (49) 33 (34) 15 (16) 1 (1)
218 (54) 152 (38) 34 (8) –
27 (28)
73 (18)
1 (1) 2 (2) 86 (90) 7 (7)
72 (18) 14 (3) 287 (71) 31 (8)
29 (30) 56 (58) 11 (11) 0
125 (31) 133 (33) 125 (31) 21 (5)
49 (51) 30 (31) 13 (14) 4 (4)
167 (41) 111 (27) 59 (15) 67 (17)
22.8 (4.0) 83 (86)
23.1 (5.1) 293 (73)
P VALUE
0.512
Baseline Demographics and Characteristics From a Paliperidone Palmitate Study in Subjects with Recent-Onset Schizophrenia or Schizophreniform Disorder By Brianne Brown, Larry Alphs, Ibrahim Turkoz, Yong Yue
Introduction • Early and effective treatment of schizophrenia may slow disease progression and improve overall patient outcomes.1 In addition, interventions specifically targeting cognitive deficits may prevent chronic disability2 • In individuals with first-episode schizophrenia, greater improvements have been reported with long-acting injections vs oral antipsychotics (APs)3,4 • The Disease Recovery Evaluation and Modification (DREaM) study is examining whether paliperidone palmitate once-monthly (PP1M) followed by paliperidone palmitate once-every-3-months (PP3M) injections can slow disease progression and possibly modify the course of schizophrenia compared with oral APs in subjects with recent-onset psychosis (schizophrenia or schizophreniform disorder) by tracking changes in cognition, functioning, and intracortical myelin volume and by tracking treatment failures • Key innovations of the DREaM study include double randomization of matched-control subjects in a delayed-start design. This study design is used to distinguish between a treatment’s effect on symptom improvement and potential disease modification5 • We describe the baseline demographics and clinical characteristics of early enrollees to the DREaM study Presented at the American Psychiatric Association Annual Meeting, May 20–24, 2017, San Diego, CA. Drs. Brown, Alphs, Yue, Janssen Scientific Affairs, LLC, Titusville, NJ; Dr. Turkoz, Janssen Research & Development, LLC, Titusville, NJ. To whom correspondence should be addressed: Dr. Larry Alphs, MD, PhD, Therapeutic Team Leader: Psychiatry, Janssen Scientific Affairs, LLC, 1125 Trenton-Harbourton Rd–A32404, Titusville, NJ 08560. E-mail: [email protected]
8 • P sychopharmacol B ull : Vol. 47 · No. 3
PB-Brown.indd 8
8/4/2017 3:38:33 PM
Baseline Demographics and Characteristics From a Paliperidone Palmitate Study
• These characteristics are compared to those of subjects enrolled in a trial evaluating a similar population: the Recovery After an Initial Schizophrenia Episode (RAISE) study, a multisite, randomized controlled trial in subjects with first-episode psychosis6 Methods Study Designs DREaM (NCT02431702) • DREaM is a prospective, matched-control, double-randomized, openlabel, flexible-dose study in subjects with recent-onset schizophrenia or schizophreniform disorder that compares disease progression and disease interception following treatment with PP1M/PP3M or oral APs • Subjects aged 18 to 35 years with a DSM-5 diagnosis of schizophrenia or schizophreniform disorder and first psychotic episode within 2 years of enrollment are eligible • Participating sites include academic- and community-based clinics both with and without established clinics that specialize in firstepisode psychosis • DREaM includes three treatment phases (Figure 1)
9 Brown, Alphs, Turkoz, et al.
RAISE • Subjects were aged 15 to 40 years with a DSM-IV diagnosis of schizophrenia, schizoaffective disorder, schizophreniform disorder, brief psychotic disorder, or psychotic disorder not otherwise specified • All participants had experienced only one episode of psychosis and had received ⩽6 months of AP medications in their lifetime • Participating sites included 34 community mental health centers in the United States • Academic centers or sites with existing first-episode psychosis programs were excluded from participation6 DREaM Screening/Baseline Eff icacy Assessments • The following assessments were performed at either screening (visit 1) or baseline (Part 1: visit 2, day 1): • Baseline demographics and clinical characteristics • MATRICS Consensus Cognitive Battery (MCCB)7: Measured key cognitive domains relevant to schizophrenia and related disorders • Personal and Social Performance (PSP) scale8: Assessed personal and social functioning within the past month P sychopharmacol B ull : Vol. 47 · No. 3
PB-Brown.indd 9
8/4/2017 3:38:33 PM
Baseline Demographics and Characteristics From a Paliperidone Palmitate Study FIGURE 1
DREaM Study Design 6FUHHQLQJ 3DUW 5XQ,Q3KDVH PRQWKRSHQODEHOQRQUDQGRPL]HG RUDO$3UXQLQSHULRG
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10 Brown, Alphs, Turkoz, et al.
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Notes: In Part 1, subjects who tolerate paliperidone extended-release but whose clinician finds it inadequately efficacious (per clinical judgment) may be switched to another protocol-specified oral AP: aripiprazole, haloperidol, olanzapine, perphenazine, quetiapine, or risperidone. In Parts 2 and 3, 9-month paliperidone palmitate treatment = PP1M for 4 months (five injections) followed by PP3M for 5 months (two injections).
• Clinical Global Impression of Severity (CGI-S) scale9: Rated the severity of the subject’s overall clinical condition on a 7-point scale (1 = not ill, 7 = extremely ill) • Medication Satisfaction Questionnaire (MSQ) 10,11: Rated selfreported satisfaction with current AP treatment on a 7-point Likert scale (1 = extremely dissatisfied, 7 = extremely satisfied) • Clinician-Rated Dimensions of Psychosis Symptom Severity (CRDPSS)12: An 8-item measure that assesses the severity of mental health symptoms that are important across psychotic disorders, such as delusions, hallucinations, disorganized speech, abnormal psychomotor behavior, negative symptoms, impaired cognition, depression, and mania, on a 5-point scale (0 = none, 4 = present and severe) Statistical Analyses • Baseline demographics and clinical characteristics were generated for the DREaM study using descriptive statistics. In some cases where data were available, demographics and clinical characteristics were compared between the DREaM and RAISE studies • Study comparisons for available data points were carried out using either the chi-squared test for categorical data or the t-test for continuous data points P sychopharmacol B ull : Vol. 47 · No. 3
PB-Brown.indd 10
8/4/2017 3:38:33 PM
Baseline Demographics and Characteristics From a Paliperidone Palmitate Study TABLE 1
Baseline Demographics in the DREaM and RAISE Studies
BASELINE CHARACTERISTIC
Age, y, mean (SD) Sex, male, n (%) Race, n (%) White Black Other Missing data Ethnicity, n (%) Hispanic or Latino Living status, n (%) Independent living Supported or structured With family/friends Homeless/other Patient education, n (%) Some college or higher Completed high school Some high or grade school No school or unknown Maternal education, n (%) Some college or higher Completed high school Some high or grade school No school or unknown
Abbreviation: SD, standard deviation.
DREaM: ENROLLED SUBJECTS N = 96
RAISE: FINAL POPULATION6 N = 404
47 (49) 33 (34) 15 (16) 1 (1)
218 (54) 152 (38) 34 (8) –
27 (28)
73 (18)
1 (1) 2 (2) 86 (90) 7 (7)
72 (18) 14 (3) 287 (71) 31 (8)
29 (30) 56 (58) 11 (11) 0
125 (31) 133 (33) 125 (31) 21 (5)
49 (51) 30 (31) 13 (14) 4 (4)
167 (41) 111 (27) 59 (15) 67 (17)
22.8 (4.0) 83 (86)
23.1 (5.1) 293 (73)
P VALUE
0.512
